Landiolol for Rate Control in Decompensated Heart Failure Due to Atrial Fibrillation

Atrial Fibrillation Clinical Trial

— LARISA  

Official title:

Landiolol for Rate Control in Decompensated Heart Failure Due to Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04694092
• Other study ID #: LARISA2020
• Status: Recruiting
• Phase: N/A
• Start date: November 5, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2021
• Source: Institute for Clinical and Experimental Medicine
• Contact: Marek Sramko, MD., PhD.
• Phone: +420776246127
• Email: marek.sramko[@]ikem.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will include patients with acute heart failure with reduced left ventricular ejection fraction (<40%) triggered by atrial fibrillation (AF) with a heart rate of >130/min. Patients in cardiogenic shock, critical state, or patients requiring emergent electric cardioversion during the first 2 hours will be excluded. The patients will be randomized (1:1) to a strategy of initial intensive heart rate control using continuous infusion of landiolol and boluses of digoxin vs. standard approach to the rate control without the use of landiolol. All patients will receive recommended pharmacotherapy of acute heart failure (diuretics, nitrates, inotropes in patients with signs of low cardiac output - preferentially milrinone or levosimendan). The patients will undergo hemodynamic monitoring, laboratory testing, evaluation of symptoms, and quantification of lung water content by ultrasound for 48 hours. The study will test a hypothesis whether patients treated with initial intensive heart rate control with the preferential use of landiolol will achieve faster heart rate control, compensation of heart failure, and relief of heart failure symptoms without causing hypotension or deterioration of heart failure.

Description:

Procedure:

1. Eligible patients with signed consent will be enrolled.

2. Baseline transthoracic echocardiography, laboratory testing, evaluation of subjective dyspnea, lung water by ultrasound, chest x-ray, hemodynamic monitoring (details below)

3. Randomisation 1:1 to standard therapy vs. intensive heart rate control

4. Two hours of therapy with continous hemodynamic monitoring (blood pressure by arterial line, cardiac output and stroke volume non-invasively by bioreactance)

1. Standard therapy (oral or intravenous beta-blockers other than landiolol while avoiding hypotension or deterioration of hemodynamics, according to the preference of the physician) with a bolus of 250-500mg of digoxin

2. Intensive heart rate control with the goal to achieve heart rate <115 during the first the hours, preferentially with continuous infusion of landiolol and a bolus of 250-500mg of digoxin. The dose will be titrated according to the actual heart rate and hemodynamic parameters (blood pressure, cardiac index, stroke volume index). If possible, in both groups, electric cardioversion will be preferentially delayed during the first 2 hours. Both groups will receive standard therapy of acute heart failure (diuretics, inotropes if needed-preferentially milrinone or levosimendan, nitrates..)

5. At 2 hours: evaluation of patients subjective dyspnea (primary clinical endpoint), heart rate (primary endpoint), hearth rhythm and hemodynamics

6. After 2 hours, both groups can be treated according to the preference of the physician.

7. Symptoms, heart rate control, hemodynamics and lung congestion will be reevaluated at 12 and 48 hours

8. The study protocol will end after 48 hours.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• acute heart failure with reduced left ventricular ejection (<40%)

• atrial fibrillation with heart rate >130/min lasting presumably >12 hours and presumably contributing to the acute heart failure

• pulmonary congestion detected by auscultation, lung ultrasound or CXR

Exclusion Criteria:

• ongoing type 1. myocardial infarction

• cardiogenic shock

• presumed need for mechanical heart support during the first 48hours of the study

• presumed need for electric cardioversion during the first 2 hours of the study

• medication for heart rate control (beta-blockers, calcium channel blockers, digoxin) or antiarrhythmics introduced <24 hours before the study. Chronic therapy with these will not be a contraindication for the study

• thyreotoxicosis

Related Conditions & MeSH terms

• Acute Heart Failure
• Atrial Fibrillation
• Atrial Fibrillation Rapid
• Heart Failure
• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Drug:
• Intensive heart rate control with landiolol
Intensive heart rate control preferably with the use of short-acting betablocker landiolol in combination with digoxin
• Standard approach to heart rate control
Standard heart rate control with intravenous or oral beta-blockers and/or antiarrhythmic in combination with digoxin

Locations

Country	Name	City	State
Czechia	Institute for Clinical and Experimental Medicine (IKEM)	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heart rate control	Achievement of heart rate <115/min for at least 15 mins	during the first 2 hours
Primary	Change in patient-reported symptoms	Change of patient-reported dyspnea evaluated 1-10 visual analog scale (1=unbearable dyspnea, 10=no symptoms)	at 2 hours
Secondary	Significant change of heart rate	Decrease of heart rate >20% from baseline	During the first 2 hours
Secondary	Heart rate and heart rhythm	the mean heart rate obtained from three measurements	heart rate measured at hours 2, 12 and 48 of the study protocol
Secondary	Safety - hypotension	Occurence of hypotension requiring reduction of the dose of betablockers or vasopressors	first 2 hours
Secondary	Change in cardiac index	Change in cardiac index (L/m2) evaluated noninvasively by bioreactance (Starling SV, Cheetah Medical)	evaluated between baseline and hour 2
Secondary	Change in stroke volume index	Change in stroke volume index (ml/m2) evaluated noninvasively by bioreactance (Starling SV, Cheetah Medical)	evaluated between baseline and hour 2